PMID- 23555025
OWN - NLM
STAT- MEDLINE
DCOM- 20130924
LR  - 20240313
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 3
DP  - 2013
TI  - Cell-free culture supernatant of Bifidobacterium breve CNCM I-4035 decreases 
      pro-inflammatory cytokines in human dendritic cells challenged with Salmonella 
      typhi through TLR activation.
PG  - e59370
LID - 10.1371/journal.pone.0059370 [doi]
LID - e59370
AB  - Dendritic cells (DCs) constitute the first point of contact between gut 
      commensals and our immune system. Despite growing evidence of the 
      immunomodulatory effects of probiotics, the interactions between the cells of the 
      intestinal immune system and bacteria remain largely unknown. Indeed,, the aim of 
      this work was to determine whether the probiotic Bifidobacterium breve CNCM 
      I-4035 and its cell-free culture supernatant (CFS) have immunomodulatory effects 
      in human intestinal-like dendritic cells (DCs) and how they respond to the 
      pathogenic bacterium Salmonella enterica serovar Typhi, and also to elucidate the 
      molecular mechanisms involved in these interactions. Human DCs were directly 
      challenged with B. breve/CFS, S. typhi or a combination of these stimuli for 4 h. 
      The expression pattern of genes involved in Toll-like receptor (TLR) signaling 
      pathway and cytokine secretion was analyzed. CFS decreased pro-inflammatory 
      cytokines and chemokines in human intestinal DCs challenged with S. typhi. In 
      contrast, the B. breve CNCM I-4035 probiotic strain was a potent inducer of the 
      pro-inflammatory cytokines and chemokines tested, i.e., TNF-alpha, IL-8 and RANTES, 
      as well as anti-inflammatory cytokines including IL-10. CFS restored TGF-beta levels 
      in the presence of Salmonella. Live B.breve and its supernatant enhanced innate 
      immune responses by the activation of TLR signaling pathway. These treatments 
      upregulated TLR9 gene transcription. In addition, CFS was a more potent inducer 
      of TLR9 expression than the probiotic bacteria in the presence of S. typhi. 
      Expression levels of CASP8 and IRAK4 were also increased by CFS, and both 
      treatments induced TOLLIP gene expression. Our results indicate that the 
      probiotic strain B. breve CNCM I-4035 affects the intestinal immune response, 
      whereas its supernatant exerts anti-inflammatory effects mediated by DCs. This 
      supernatant may protect immune system from highly infectious agents such as 
      Salmonella typhi and can down-regulate pro-inflammatory pathways.
FAU - Bermudez-Brito, Miriam
AU  - Bermudez-Brito M
AD  - Department of Biochemistry and Molecular Biology II, Institute of Nutrition and 
      Food Technology Jose Mataix, Biomedical Research Center, University of Granada, 
      Granada, Spain.
FAU - Munoz-Quezada, Sergio
AU  - Munoz-Quezada S
FAU - Gomez-Llorente, Carolina
AU  - Gomez-Llorente C
FAU - Matencio, Esther
AU  - Matencio E
FAU - Bernal, Maria J
AU  - Bernal MJ
FAU - Romero, Fernando
AU  - Romero F
FAU - Gil, Angel
AU  - Gil A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130312
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Cytokines)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (TLR9 protein, human)
RN  - 0 (TOLLIP protein, human)
RN  - 0 (Toll-Like Receptor 9)
RN  - EC 2.7.11.1 (IRAK4 protein, human)
RN  - EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (Caspase 8)
SB  - IM
MH  - Bifidobacterium/*physiology
MH  - Caspase 8/genetics/immunology
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Culture Media, Conditioned/*pharmacology
MH  - Cytokines/genetics/*immunology
MH  - Dendritic Cells/cytology/*drug effects/immunology
MH  - Gene Expression Regulation
MH  - Human Umbilical Vein Endothelial Cells/cytology
MH  - Humans
MH  - Interleukin-1 Receptor-Associated Kinases/genetics/immunology
MH  - Intracellular Signaling Peptides and Proteins/genetics/immunology
MH  - Probiotics/*pharmacology
MH  - Salmonella typhi/growth & development/*immunology
MH  - Signal Transduction
MH  - Toll-Like Receptor 9/genetics/immunology
PMC - PMC3595273
COIS- Competing Interests: Esther Matencio, Maria J. Bernal, and Fernando Romero are 
      members of the Hero Institute for Infant Nutrition, Hero Spain S. A. The sponsor 
      had no role in the biological sample analysis, statistical analysis or data 
      interpretation. This does not alter the authors' adherence to all the PLOS ONE 
      policies on sharing data and materials.
EDAT- 2013/04/05 06:00
MHDA- 2013/09/26 06:00
PMCR- 2013/03/12
CRDT- 2013/04/05 06:00
PHST- 2012/11/15 00:00 [received]
PHST- 2013/02/13 00:00 [accepted]
PHST- 2013/04/05 06:00 [entrez]
PHST- 2013/04/05 06:00 [pubmed]
PHST- 2013/09/26 06:00 [medline]
PHST- 2013/03/12 00:00 [pmc-release]
AID - PONE-D-12-36145 [pii]
AID - 10.1371/journal.pone.0059370 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(3):e59370. doi: 10.1371/journal.pone.0059370. Epub 2013 Mar 12.